DMT1 overexpression exacerbates Aβoligomer-induced cell damage

This study aims to reveal the role of metal ion transporter DMT1 in neurotoxicity induced by Aβ142 oligomers.We exposed SH-SY5Y cells(S-DMT1)stably overexpressing the DMT1 gene and SH-SY5Y cells(SGFP)overexpressing empty green fluorescent protein to AB.42 oligomers.CCK8 and Hoechst 33258 were used to detect the cell death rate and apoptotic rate.W estern blotting was used to detect the levels of apoptotic proteins caspase-3,Bax and Bcl-2.The results of CCK8 experiments showed that compared with SGFP cells,the number of viable cells in S-DMT1 cells after Aβ42 oligomer treatment was significantly reduced.Heochst33258 staining results showed that the rate of nuclear shrinkage in S-DMT1 cells treated with Aβ142 oligomer was significantly higher than that in SGFP group.Moreover,the levels of caspase-3 and Bax proteins in S-DMT1 cells were higher than those in SGFP group,while BcI-2 decreased after Aβ42 oligomers.DMT1 overexpression increases the toxic effects of Aβ42 oligomers by promoting apoptosis.4.Regulation of"P35/P25-CDK5-Tau"signaling pathway in hippocampi and prefrontal cortex of AD rats by electroacupuncture.

益智胶囊对阿尔茨海默病大鼠学习记忆能力的改善作用

目的:探讨益智胶囊对海马注射β淀粉样蛋白(1-42)(Aβ1-42)引起阿尔茨海默病(AD)大鼠学习记忆能力和胆碱能系统以及Tau蛋白磷酸化水平的影响。方法:将SD大鼠随机分为正常组、假手术组、模型组、阳性药石杉碱甲组、益智胶囊(低、中、高)3个剂量组,假手术组右侧海马单次注射生理盐水5μL,模型组、阳性药组及益智胶囊各组分别右侧海马单次注射Aβ1-42(2 g·L-1)5μL,益智胶囊组和阳性药组用益智胶囊提取物(1.78,3.56,7.12 g·kg-1)和石杉碱甲(60μg·kg-1)连续灌胃给药31 d,1次/d,其余3组同样方法给予生理盐水。给药21 d后,以Morris水迷宫实验测试各组大鼠学习记忆能力,连续10 d,训练期间继续给药;水迷宫实验结束后,生化检测胆碱乙酰转移酶(Ch AT)和乙酰胆碱酯酶(Ach E)的活性;Western blot法定量检测海马神经元Aβ蛋白表达变及Tau蛋白(Ser262)的磷酸化程度。结果:与正常对照组相比,假手术组的游泳总路程和逃避潜伏期未见明显统计学差异;与假手术组相比,模型组的游泳总路程和逃避潜伏期均明显延长,且均具有统计学差异;与模型组相比,其他各组AD大鼠的游泳总路程和逃避潜伏期均明显缩短,空间探索试验给药组穿越站台的次数明显增加;与模型组相比,给药组Ach E活性降低,Ch AT活性升高;Aβ蛋白的表达和Tau(S262)磷酸化水平均降低。结论:益智胶囊能改善Aβ1-42引起的AD大鼠学习记忆障碍,其作用机制可能是增加中枢胆碱能系统Ach的含量和抑制Tau蛋白过度磷酸化。